Very High Dose Cytarabine as Salvage Therapy for Relapsed or Refractory Acute Myeloid Leukemia in the Setting of Intensified Anthracycline Induction and Post Stem-Cell Transplantation

Purpose Intensification by high-dose cytarabine in postremission or induction therapy and prolonged maintenance are established strategies to improve the outcome in patients with acute myeloid leukemia (AML). Whether additional intensification can add to this effect has not yet been determined. Patients and Methods A total of 1,770 patients (age 16 to 85 years) with de novo or secondary AML or high-risk myelodysplastic syndrome (MDS) were randomly assigned upfront for induction therapy containing one course with standard dose and one course with high-dose cytarabine, or two courses with high-dose cytarabine, and in the same step received postremission prolonged maintenance or busulfan/cyclophosphamide chemotherapy with autologous stem-cell transplantation. Results The complete remission rate in patients younger than 60 and ≥ 60 years of age was 70% and 53%, respectively. The overall survival at 3 years in the two age groups was 42% and 19%, the relapse-free survival was 40% and 19%, and the ongoing remission duration was 48% and 22%, respectively. There were no significant differences in these results between the two randomized induction arms or between the two postremission therapy arms. There was no significant difference in any prognostic subgroup according to secondary AML/MDS, cytogenetics, WBC, lactate dehydrogenase, and early blast clearance. Conclusion The regimen of one course with standard-dose cytarabine and one course with high-dose cytarabine for induction, and prolonged maintenance for postremission chemotherapy in patients with AML is not improved by additional escalation in cytotoxic treatment.

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Effect of postremission high dose cytarabine-based consolidation chemotherapy before allogenic stem cell transplantation in outcomes of acute myeloid leukemia patients

Transfusion and Apheresis Science ◽

10.1016/j.transci.2018.09.013 ◽

2018 ◽

Vol 57 (6) ◽

pp. 752-755 ◽

Cited By ~ 1

Author(s):

Rafiye Ciftciler ◽

Haluk Demiroglu ◽

Yahya Buyukasık ◽

Mufide Okay ◽

Salih Aksu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

High Dose ◽

Consolidation Chemotherapy ◽

Allogenic Stem Cell Transplantation ◽

High Dose Cytarabine ◽

Acute Myeloid

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Interleukin-2 After Autologous Stem-Cell Transplantation for Adult Patients With Acute Myeloid Leukemia in First Complete Remission

Journal of Clinical Oncology ◽

10.1200/jco.2003.12.125 ◽

2003 ◽

Vol 21 (4) ◽

pp. 615-623 ◽

Cited By ~ 26

Author(s):

Anthony S. Stein ◽

Margaret R. O’Donnell ◽

Marilyn L. Slovak ◽

David S. Snyder ◽

Auayporn P. Nademanee ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Interleukin 2 ◽

Cumulative Probability ◽

High Dose ◽

High Dose Cytarabine ◽

Acute Myeloid

Purpose: To determine the disease-free survival (DFS) and toxicity of administering interleukin-2 (IL-2) immunotherapy early after autologous stem-cell transplantation (ASCT) to simulate a graft versus leukemia effect observed in allogeneic transplantation. Patients and Methods: Fifty-six patients with acute myeloid leukemia in first remission received a single consolidation of high-dose cytarabine-idarubicin at a median of 1.1 month postremission with the intent to proceed to ASCT and IL-2 9 × 106 U/m2/24 h for 4 days, followed by 10 days of IL-2 1.6 × 106 U/m2/24 h on hematologic recovery. Results: Eighty-four percent of patients received the intended ASCT, and 68% of patients received IL-2 treatment. With a median follow-up of 39.4 months (range, 1.2 to 76.3 months), the 2-year cumulative probability of DFS for all 56 patients is 68% (95% confidence interval [CI], 55% to 80%) and 74% (95% CI, 57% to 85%) for the 39 patients undergoing IL-2 treatment after ASCT. The 2-year cumulative probability of DFS for favorable, intermediate, and unfavorable cytogenetics is 88% (95% CI, 59% to 97%), 48% (95% CI, 26% to 67%), and 70% (95% CI, 23% to 93%), respectively. Toxicities from IL-2 were mainly thrombocytopenia, leukopenia, fever, and fluid retention. Two septic deaths occurred during neutropenia, which includes one during consolidation and one during transplant, for an overall 4% mortality rate. Conclusion: These results suggest that a moderate dose of IL-2 after high-dose cytarabine-idarubicin–mobilized ASCT is associated with a low regimen-related toxicity and may improve DFS. A phase III study of IL-2 is now warranted.

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A Second Course of High-Dose Cytarabine before Autologous Stem Cell Transplantation Does Not Improve Outcome of Young Acute Myeloid Leukemia Patients in First Complete Remission: Results of the BGMT 95 Study.

Blood ◽

10.1182/blood.v104.11.5194.5194 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5194-5194

Author(s):

Eric Jourdan ◽

Françoise Rigal-Huguet ◽

Gérald Marit ◽

Norbert Vey ◽

Nicole Dastugue ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Cumulative Incidence ◽

Myeloid Leukemia ◽

High Dose ◽

High Dose Cytarabine ◽

Wbc Count ◽

Acute Myeloid

Abstract Background. Once complete remission (CR) is achieved in young (18–60) acute myeloid leukemia (AML) patients (pts), the main question is about the best post remission treatment. For pts not eligible for allogeneic bone marrow transplantation (AlloBMT) high-dose cytarabine-based chemotherapy (HiDAC) followed by autologous stem cell transplantation (ASCT) is an interesting option. However, the number of courses of cytarabine to apply before ASCT is not determined. The aim of this randomized study was to evaluate the impact of a second HiDAC before ASCT. Pts and methods. Pts received an induction by daunorubicine 60 mg/m2/d 3d + cytarabine 100 mg/m2/d (CI) 10 d. followed by a consolidation based on cytarabine 50 mg/m2/12h SC 7d + daunorubicine 60 mg/m2/d 2d. Pts < 45 with a sibling donor had an alloBMT (cyclophosphamide 60 mg/kg IV 2d + fractionated TBI 12 Gy). The others had a superconsolidation (cytarabine 3 g/m2/12h IV 4d + daunorubicine 45 mg/m2/d) followed by stem cell collection (either BM or PBSC). Then was the randomization between ASCT (busulfan 4 mg/kg/d po 4d + melphalan 140 mg/m2 on d5) immediately (SC1 group) or after 1 more course of HiDAC (cytarabine 3 g/m2/12h IV 4d) (SC2 group). Results. Between 05.1995 and 02.2001 a total of 437 pts entered the study. The median age of these pts (M/F = 238/199) was 47 years (18–60) with 203 of them under 45. Median WBC count was 12.5 (0.2–335) and WBC was > 30 109/L for 140 pts. The FAB distribution was: M1/M2 = 227; M4/M5 = 151; M0/M6/M7 = 59. The cytogenetics risk groups distribution was: low risk = 56 (13.8%); intermediate risk = 265 (65.4%); high risk = 84 (20.8%). CR was achieved in 2 courses for 46 pts (10.5 %). Out of the 437 initial pts, 351 achieved CR (80 %), 65 were eligible for alloBMT, 277 for randomization, and 128 were randomized (65 for SC1, 63 for SC2). The only difference between randomized and non-randomized pts was for number of course to achieve CR (7 % vs 16.8 % respectively, p = .01). This turn into a difference for cumulative incidence of non relapse deaths (CINRD) (8.7 % vs 20.6 % ; p = .01) but not for cumulative incidence of relapse (CIR). Overall survival (OS), leukemia free survival (LFS) and CIR and CINRD were 57.7, 50.9, 35.5, 19.9 for alloBMT. For SC1/SC2 results were : 41.3/53.7 for OS (p = .10), 39.2/49.6 for LFS (p = .11), 56.7/45.1 for CIR (p = .08), 8.5/8.4 for CINRD (p = .95). Multivariate analysis for LFS showed the independent impact of initial WBC count, cytogenetics and number of course to achieve CR. However, type of treatment (SC1 vs SC2) had no impact on LFS (p = .41). This lead us to conclude that one course of HiDAC was enough before ASCT despite the rather low proportion of randomized pts.

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